A trend toward minimally invasive therapy is apparent throughout the field of obstetrics and gynecology, with pressure from third party payers to reduce costs and a desire to speed therapy and minimize adverse effects on work productivity. Improvement in the pregnancy rate following in vitro fertilization can be a significant step toward this goal.
In vitro fertilization (IVF) involves the production of embryos outside the uterus with subsequent placement of the embryos into the uterus or fallopian tubes. Traditional techniques include ultrasound-guided transvaginal retrieval of eggs or oocytes followed by insemination with sperm obtained by masturbation. Transfer of embryos into the uterine or endometrial cavity typically occurs after culturing the embryos in vitro for 48 hours.
Traditional embryo transfer involves placement of up to eight embryos in 10 to 30 microliters of medium into a polytetrafluoroethylene or "TEFLON.TM." catheter. The catheter passes through the cervical opening into the endometrial cavity. Subsequently the medium containing the embryos is discharged into the endometrial cavity. The procedure is performed blindly without visualizing the catheter tip or endometrium. The patient typically rests in the prone position for two hours following the transfer.
Several problems can arise with conventional embryo transfer. First, the embryos are relatively mobile following transfer. They are sometimes found attached to the catheter or in the cervix or vagina. They can also travel into the fallopian tube, as demonstrated by a higher rate of tubal gestation following in vitro fertilization as compared to normal conception.
Contractions and peristalsis of the uterine musculature produce movement of intrauterine fluids as demonstrated both radiographically and ultrasonically. Motion of embryos in this fluid can interfere with implantation. In addition, transcervical transfer disrupts the cervical mucous plug which normally prevents loss of embryos. Thus numerous mechanisms may contribute to embryo loss following conventional embryo transfer.
Another factor preventing pregnancies after enmbryo transfer is poor endometrial receptivity, both from hormonal over-stimulation of the endometrium and intrinsic anatomic defects. Use of hormones such as gonadotropins to stimulate follicular development causes poorly receptive endometrium by elevating estradiol levels and over-stimulating endometrial development. Electron microscopy has revealed excessive development of the ciliary border of the endometrium and clinical experience shows an increase in endometrial secretions with gonadotropin stimulation. Several classes of patients have distinct anatomic abnormalities affecting implantation capacity. Examples include myomas encroaching on the uterine cavity, uterine septa, endometrial polyps, and diethylstilbestrol (DES) exposure with its attendant defects, adhesions, vascular anomalies and endometritis. Age is also associated with decreased endometrial receptivity. If endometrial receptivity is inadequate, normal embryos are less likely to implant and produce pregnancy.
A mathematical model has been developed for pregnancy rates as a result of in vitro fertilization. The equation is: EQU PR=EQ.times.ER.times.TE.times.N,
where
PR=Pregnancy rate, PA0 EQ=Embryo quality, PA0 ER=Endometrial receptivity, PA0 TE=Embryo transfer efficiency, and PA0 N=Number of embryos transferred.
See Paulson, et al. "Factors affecting embryo implantation after human in vitro fertilization: A hypothesis," Am. J. Obstet. Gynecol., 163(6) 1:2020 (1990). By analysis and comparison of natural cycles, where endometrial receptivity should be ideal, with oocyte donor cycles, where embryo quality should be ideal, embryo transfer efficiency has been estimated at approximately 60%. A typical IVF cycle with embryo quality of 25%, endometrial receptivity of 50%, and transfer of four embryos, gives a pregnancy rate of roughly 30% per embryo transfer (0.25.times.0.50.times.0.6.times.4=0.3). This is typical of a good IVF program. However, if transfer efficiency improved to 90%, pregnancy rates would rise by 50%, yielding a pregnancy rate of 45% per embryo transfer (0.25.times.0.5.times.0.9.times.4=0.45).
Improving the results of in vitro fertilization depends in part on improving embryo transfer efficiency. A variety of transfer techniques are available, but they provide no more than 60% transfer efficiency. Current catheter and fiberoptic technology allows the development of better catheters and mechanisms for directly visualizing the endometrium. These technologies may enable treatment and superior management of the earliest stage of pregnancy, the time of implantation.
Hysteroscopy, or fiberoptic endoscopy of the uterus and/or fallopian tubes, has been used for transfer of gametes, sperm and/or ova to the fallopian tube for in vivo fertilization. Thus, hysteroscopy can be performed for the purpose of transferring gametes without significantly disrupting the endometrium or injuring the gametes. Catheters and hysteroscopes used in conjunction with the invention are composed of biologically inert materials used in Class III medical devices. A Class III medical device is allowed temporary direct blood conrace, generally for less than 24 hours.